Association Between Exposure to Phenols and Parabens and Allergy-Related Outcomes.

Advanced data mining approaches in the assessment of urinary concentrations of bisphenols, chlorophenols, parabens and benzophenones in Brazilian children and their association to DNA damage

A rapid and sensitive method based on ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the simultaneous determination of 12 typical personal care products (PCPs) in human urine. These PCPs included five paraben preservatives (PBs), five benzophenone UV absorbers (BPs), and two antibacterial agents. Accordingly, 1 mL of the urine sample was mixed with 500 μL of β-glucuronidase-ammonium acetate buffer solution (enzymatic activities are 500 units/mL) and 75 μL of a mixed internal standard working solution (internal standard contents are 7.5 ng), followed by enzymatic hydrolysis overnight (≥16 h) at 37 ℃ in a water bath. The 12 targeted analytes were enriched and cleaned up using an Oasis HLB solid phase extraction column. Separation was performed on an Acquity BEH C18 column (100 mm×2.1 mm, 1.7 μm) using an acetonitrile-water system as the mobile phase, in negative electrospray ionization (ESI-) multiple reaction monitoring (MRM) mode, for target detection and stable isotope internal standard quantification. The optimal MS conditions were established by optimizing the instrument parameters and comparing two analytical columns (Acquity BEH C18 and Acquity UPLC HSS T3) as well as different types of mobile phases (methanol or acetonitrile as the organic phase) to achieve better chromatographic separation. In order to obtain higher enzymatic and extraction efficiency, different enzymatic conditions, solid phase extraction columns, and elution conditions were investigated. The final results showed that methyl parabens (MeP), benzophenone-3 (BP-3), and triclosan (TCS) showed good linearities in the ranges of 4.00-800, 4.00-800 and 5.00-200 μg/L, respectively, the other targeted compounds showed good linearities in the ranges of 1.00-200 μg/L. The correlation coefficients were all greater than 0.999. The method detection limits (MDLs) were in the range of 0.06-1.09 μg/L, and the method quantification limits (MQLs) ranged from 0.08 to 3.63 μg/L. At three spiked levels, the average recoveries of the 12 targeted analytes ranged from 89.5% to 111.8%. The intra-day and inter-day precisions were 3.7%-8.9% and 2.0%-10.6%, respectively. The results of the matrix effect assessment showed that MeP, ethyl paraben (EtP), and benzophenone-2 (BP-2) exhibited strong matrix effects (26.7%-103.8%); propyl paraben (PrP) exhibited moderate matrix effects (79.2%-112.0%); and the other eight target analytes exhibited weak matrix effects (83.3%-113.8%). The matrix effects of the 12 targeted analytes after correction using the stable isotopic internal standard method ranged from 91.9% to 110.1%. The developed method was successfully applied to the determination of the 12 PCPs in 127 urine samples. Ten typical PCPs were detected, with the overall detection rates ranging from 1.7% to 99.7%, except for benzyl paraben (BzP) and benzophenone-8 (BP-8). The results revealed that the population in this area was widely exposed to PCPs, especially MeP, EtP and PrP; the detection rates and concentrations of these PCPs were found to be very high. Our analytical method is simple and sensitive, and it is expected to be an effective tool for biomonitoring PCPs in human urine samples as part of environmental health studies.

Parabens and triclosan in red swamp crayfish (Procambarus clarkii) from China: Concentrations, tissue distribution and related human dietary intake risk

BackgroundEpidemiologic studies of the effects of parental preconception paraben exposures on child behavior are limited despite emerging evidence suggesting that such exposures may affect offspring neurodevelopment.ObjectiveWe investigated whether maternal and paternal preconception and maternal pregnancy urinary concentrations of parabens were associated with child behavior.MethodsWe analyzed data from the Preconception Environmental exposure And Childhood health Effects Study, an ongoing prospective cohort of children aged 6–13 years and their parents. We estimated covariate‐adjusted associations of loge‐transformed urinary methyl, propyl, and butyl paraben concentrations (individually using linear regression models and as a mixture using quantile g‐computation) collected prior to conception and during pregnancy with Behavioral Assessment System for Children‐3 and Behavior Rating Inventory of Executive Function T‐scores (higher scores indicate more problem behaviors).ResultsThis analysis included 140 mothers, 81 fathers, and 171 children (25 sets of twins); parents were predominantly non‐Hispanic white (88% for both mothers and fathers). In single paraben models, higher paternal preconception urinary propyl and methyl paraben concentrations were associated with higher Internalizing Problem T‐scores (propyl paraben β= 1.7; 95% confidence interval: 0.6, 2.8, methyl paraben β= 2.2; 95% confidence interval: 0.5, 3.9) and higher Behavioral Symptom Index T‐scores (propyl paraben β= 1.4; 95% confidence interval: 0.3, 2.5, methyl paraben β= 1.6; 95% confidence interval: ‐0.1, 3.3). Each quantile increase in the paternal mixture of three parabens was associated with a 3.4 (95% confidence interval: 0.67, 6.1) and 2.5 (95% confidence interval: 0.01, 5.0) increased internalizing problem and Behavioral Symptom Index T‐scores respectively. Higher paternal preconception (β= 1.0; 95% confidence interval: 0.04, 1.9) and maternal preconception (β= 1.1 95% confidence interval: ‐0.1, 2.2) concentrations of propyl paraben were associated with higher Behavior Rating Inventory of Executive Function Metacognition Index T‐scores in children, but the paraben mixtures was not.ConclusionIn this cohort, paternal preconception urinary concentrations of propyl and methyl paraben were associated with worse parent‐reported child behaviors.

The associations between personal care products use and urinary concentrations of phthalates, parabens, and triclosan in various age groups: The Korean National Environmental Health Survey Cycle 3 2015–2017

Phenols and parabens are two classes of high production volume chemicals that are used widely in consumer and personal care products and have been associated with reproductive harm and pregnancy complications, such as preeclampsia and gestational diabetes. However, studies examining their influence on maternal blood pressure and gestational hypertension are limited. We investigated associations between individual phenols, parabens, and their mixture on maternal blood pressure measurements, including systolic and diastolic blood pressure (SBP and DBP) and hypertension during pregnancy (defined as stage 1 or 2 hypertension), among Puerto Rico PROTECT study participants. We examined these relationships cross-sectionally at two time points during pregnancy (16-20 and 24-28 wks gestation) and longitudinally using linear mixed models (LMMs). Finally, we used quantile g-computation to examine the mixture effect on continuous (SBP, DBP) and binary (hypertension during pregnancy) blood pressure outcomes. We observed a trend of higher odds of hypertension during pregnancy with exposure to multiple analytes and the overall mixture [including bisphenol A (BPA), bisphenol S (BPS), triclocarbon (TCC), triclosan (TCS), benzophenone-3 (BP-3), 2,4-dichlorophenol (2,4-DCP), 2,5-dichlorophenol (2,5-DCP), methyl paraben (M-PB), propyl paraben (P-PB), butyl paraben (B-PB), and ethyl paraben (E-PB)], especially at 24-28 wk gestation, with an adjusted mixture (95% CI: 1.03, 2.38). Lower SBP and higher DBP were also associated with individual analytes, with results from LMMs most consistent for methyl paraben (M-PB) or propyl paraben (P-PB) and increased DBP across pregnancy [adjusted M-PB (95% CI: 0.17, 1.38) and adjusted P-PB (95% CI: 0.19, 1.51)] and for BPA, which was associated with decreased SBP (adjusted ; 95% CI: , ). Consistent with other literature, we also found evidence of effect modification by fetal sex, with a strong inverse association observed between the overall exposure mixture and SBP at visit 1 among participants carrying female fetuses only. Our findings indicate that phenol and paraben exposure may collectively increase the risk of stage 1 or 2 hypertension during pregnancy, which has important implications for fetal and maternal health. https://doi.org/10.1289/EHP14008.

Exposure and potential risks of thirteen endocrine- disrupting chemicals in pharmaceuticals and personal care products for breastfed infants in China

Are in-utero or peripubertal exposures to phthalates, parabens and other phenols found in personal care products associated with timing of pubertal onset in boys and girls? We found some associations of altered pubertal timing in girls, but little evidence in boys. Certain chemicals in personal care and consumer products, including low molecular weight phthalates, parabens and phenols, or their precursors, are associated with altered pubertal timing in animal studies. Data were from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) longitudinal cohort study which followed 338 children in the Salinas Valley, California, from before birth to adolescence. Pregnant women were enrolled in 1999-2000. Mothers were mostly Latina, living below the federal poverty threshold and without a high school diploma. We measured concentrations of three phthalate metabolites (monoethyl phthalate [MEP], mono-n-butyl phthalate and mono-isobutyl phthalate), methyl and propyl paraben and four other phenols (triclosan, benzophenone-3 and 2,4- and 2,5-dichlorophenol) in urine collected from mothers during pregnancy and from children at age 9. Pubertal timing was assessed among 179 girls and 159 boys every 9 months between ages 9 and 13 using clinical Tanner staging. Accelerated failure time models were used to obtain mean shifts of pubertal timing associated with concentrations of prenatal and peripubertal biomarkers. In girls, we observed earlier onset of pubic hair development with prenatal urinary MEP concentrations and earlier menarche with prenatal triclosan and 2,4-dichlorophenol concentrations. Regarding peripubertal biomarkers, we observed: earlier breast development, pubic hair development and menarche with methyl paraben; earlier menarche with propyl paraben; and later pubic hair development with 2,5-dichlorophenol. In boys, we observed no associations with prenatal urinary biomarker concentrations and only one association with peripubertal concentrations: earlier genital development with propyl paraben. These chemicals are quickly metabolized and one to two urinary measurements per developmental point may not accurately reflect usual exposure. Associations of peripubertal measurements with parabens may reflect reverse causality: children going through puberty early may be more likely to use personal care products. The study population was limited to Latino children of low socioeconomic status living in a farmworker community and may not be widely generalizable. This study contributes to a growing literature that suggests that exposure to certain endocrine disrupting chemicals may impact timing of puberty in children. This study was funded by the National Institute of Environmental Health Sciences and the US Environmental Protection Agency. The authors declare no conflicts of interest. N/A.

BackgroundWhile the associations of indoor allergens, endotoxin, heavy metals, and parabens with allergy outcomes are well-studied, the combined association remains unclear. This study examines the association between their combined exposure and allergy outcomes in adults.MethodsA toatl of 1,065 adults from the National Health and Nutrition Examination Survey (NHANES) 2005–2006 were included in analyses. We applied a weighted logistic regression model to investigate the association between individual exposure to 10 chemicals (including Aspergillus fumigatus, Canf 1, Feld 1, Mus m 1, endotoxin, cadmium, lead, total mercury, methyl paraben, and propyl paraben) and allergy-related outcomes. WQS and BKMR models were further used to examine the combined associations.ResultsThe weighted logistic regression model indicated that high-level exposures (Tertile 3 vs. Tertile 1) to Can f 1, Fel d 1, Mus m 1, endotoxin, cadmium, mercury, methyl paraben, and propyl paraben were significantly associated with an increased risk of allergy-related outcomes. In WQS regression analysis, the WQS index was significantly associated with an increased risk of allergy-related outcomes (aOR = 1.49, 95% CI: 1.04–2.11, p = 0.027). Can f 1, methyl paraben, endotoxin and cadmium were the most heavily weighed exposure indicators. In BKMR analysis, overall risk estimates were consistently elevated relative to the 25th percentile reference and increased with higher exposure.ConclusionJoint and individual exposures to multiple environmental pollutants, particularly Can f 1, methyl paraben, endotoxin, and cadmium, are associated with increased allergy risk in adults. These results underscore the need for integrated exposure assessment in allergy prevention strategies.

Parabens are widely used as preservatives in personal care products, foodstuffs, and pharmaceuticals. Concerns have been raised regarding the potential endocrine disruption effects of parabens. In the present study, the urinary concentration of four common parabens, including methylparaben (MP), ethylparaben (EP), propylparaben (PP), and butylparaben (BP), in 100 Iranian adolescents randomly referring to health services centres were analyzed using GC/MS. The association of sociodemographic and lifestyle variables, collected through questionnaire, with the concentration of parabens also were studied. Median concentrations of MP, EP, PP, and BP were 92.21, 8.46, 12.26, and 8.42µg/g creatinine, respectively. There was a strong positive significant correlation between MP and PP (r = 0.694) and moderate to a weak correlation between the other parabens. The concentration of urinary MP in females was significantly higher than those in male (p = 0.021). There was a significant negative association between different BMI groups and MP and EP. There also was a positive significant association between the MP and age, and between MP, EP, and PP, and tobacco use. Although the estimated daily intake of the parabens was lower than the Acceptable Daily Intake, it was higher than those reported in other countries. This confirms the widespread exposure of Iranian adolescents to the paraben compounds and their association with sociodemographic factors. This was the first study reporting the urinary parabens level in Iranian adolescents, and the data can be used as a basis for assessing the risk of exposure to parabens in the Iranian population in future studies.

TPS 743: Health effects in pregnancy, Exhibition Hall, Ground floor, August 26, 2019, 3:00 PM - 4:30 PM Background/Aim: Human exposure to parabens is very common in daily life by using personal care products. These chemicals are associated with poor birth outcomes. However, modifying effects of polymorphism in glutathione S-transferases (GST) gene remain unexplored. Therefore, the aim of this study was to investigate the effect of genetic polymorphisms on the association of prenatal exposure to parabens with birth outcomes. Methods: We plan to recruit more than 300 women during 3rd stage pregnancy between 2017 and 2019 in Korean pregnant women, called The Mother And Kids Environmental health (MAKE) Study. We measured parabens (Methyl-paraben (MeP), Ethyl-paraben (EtP), Propyl-paraben (PrP)) concentrations in maternal urine samples, also collected information on birth outcome, socio-economic status, and consumption habits of consumer products. Multivariate linear regression was used to examine whether the association between prenatal exposure to parabens and birth outcomes (gestational age, birth weight, body length, head circumference and abdominal circumference) varied by maternal GST genes. Results: The adjusted geometric means for urinary concentrations of MeP, EtP, and PrP were 13.96, 9.45, and 1.70 ng/mL, respectively. Parabens were positively associated with weight and abdominal circumference at birth. In particular, MeP and PrP showed significant association with an increase in abdominal circumference (MeP, ß=0.355, p=0.02; PrP, ß=0.376, p=0.02) adjusting for potential confounders. Prenatal exposure to parabens showed significantly positive association with abdominal circumference in mother of GST null genotype (MeP, ß=0.634, p=0.02; EtP, ß=0.546, p=0.05; PrP, ß=0.618, p=0.04). Conclusions: This study reported the association between prenatal parabens exposure and birth outcomes. We also found that GST polymorphism might affect the association between prenatal parabens exposure and abdominal circumference, suggesting the effect of genetic susceptibility on the relation between prenatal parabens exposure and abdominal circumference.

In the United States, Black women are 39% more likely to die from breast cancer compared to White women (AACR Cancer Disparities Progress Report 2020). Furthermore, Black women are at a higher risk of developing breast cancer under the age of 40 than any other racial or ethnic group. While the underlying cause of these disparities is multifactorial, exposure to endocrine disrupting chemicals (EDCs) in hair and personal care products has been associated with increased risk of breast cancer. Parabens are known EDCs that are commonly used as preservatives in hair and other personal care products. The Environmental Working Group scores methylparaben (MP), propylparaben (PP), and butylparaben (BP) moderate (MP) to high (BP and PP) on a hazardous scale of chemicals found in personal care products. Furthermore, these parabens are restricted in personal care products with set maximum concentration standards in Japan, the European Union, and Southeast Asia. Studies have shown that parabens impact breast cancer cell proliferation, death, migration/invasion, and metabolism, as well as gene expression in vitro. However, these studies were conducted using cell lines of European ancestry; to date, no studies have utilized breast cancer cell lines of West African ancestry to examine effects of parabens. We hypothesize that, like what has been shown for breast cancer cell lines with European ancestry, parabens will promote pro-tumorigenic effects in breast cancer cell lines with West African ancestry. To test this hypothesis, we treated MCF-7 (European ancestry) and HCC1500 (West African ancestry) luminal breast cancer cell lines with biologically relevant doses of either MP, PP, or BP. We also co-treated with the estrogen receptor (ER) antagonist ICI 182,780 to determine whether observed effects are mediated by ER. We found BP increases HCC1500 cell viability, but not MCF-7 cell viability. This effect was not blocked by co-treatment with ICI 182,780. We also observed that BP and PP, but not MP, increased expression of estrogen-regulated genes in both MCF-7 and HCC1500. The increase in gene expression was reduced with co-treatment of ICI 182,780 in both cell lines, suggesting that these effects are ER-mediated. Preliminary studies suggest that parabens promote migration of both cell lines, with a potentially greater effect on HCC1500 cells. Taken together, these data demonstrate that parabens, particularly BP and PP, promote pro-tumorigenic effects in diverse luminal breast cancer cell lines. These findings have future translational relevance as we are part of a community-led initiative called Bench to Community. Bench to Community brings together basic researchers in endocrinology and social-behavioral scientists, community stakeholders including breast cancer survivors to develop interventions to reduce adverse exposures to EDCs in hair and other personal care products in Black women.Presentation: Sunday, June 12, 2022 12:42 p.m. - 12:47 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Parabens and triclosan in shellfish from Shenzhen coastal waters: Bioindication of pollution and human health risks

Parabens (PBs) and triclosan (TCS) are generally used as antimicrobials mostly in personal care products. Their wide prevalence in daily products raised an acute need for the biomonitoring of these contaminants and the investigation of possible health impacts. In this study we aimed to quantitatively determine PBs and TCS levels in urine and amniotic fluid samples using a liquid chromatography - mass spectrometry system (LC-MS). Ninety nine (99) pregnant women took part in this research. The samples were collected during the amniocentesis in the early second trimester of their pregnancy. Women of all ages, education, household income and profession were selected. The exposure and the burden of pregnant women and their infants were also evaluated. The most prevalent compound in urine, among the analyzed, was TCS with 74.7 % positive samples while in amniotic fluid methyl paraben (MePB) with 21.2 % positive samples. MePB was detected at higher concentrations in urine (mean: 378.5 ng/mL) followed by TCS (mean: 55.3 ng/mL), ethyl paraben (EtPB) (mean: 23.2 ng/mL) and butyl paraben (BuPB) (mean: 2.3 ng/mL) while benzyl paraben (BePB) was not detected in any urine sample. Concentrations in amniotic fluid samples were much lower. In particular, the mean concentrations were 6.6 ng/mL for MePB, 9.2 ng/mL for EtPB, 0.4 ng/mL for BuPB, 0.6 ng/mL for BePB and 1.8 ng/mL for TCS. The detected levels of all analytes in urine were correlated with those in amniotic fluid but no statistically significant results arose (p >n0.05). Negative associations were observed between amniotic fluid levels of MePB and maternal age (p = 0.05) while both urinary and amniotic levels of TCS were correlated with maternal BMI (p = 0.04). Somatometric characteristics of the infants showed no statistical significant associations with the detected levels of PBs and TCS. This study indicated a strong/possible association between exposure of pregnant women to TCS and higher/lower maternal body weight gain during pregnancy. The same trend was observed between amniotic fluid MePB levels and maternal age. However, no statistically significant associations were observed between neonatal somatometric characteristics or health status and PBs and TCS levels.

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